Metabolites involved in glycolysis and amino acid metabolism are altered in short children born small for gestational age.

Autor: Murray PG; Institute of Human Development, University of Manchester, Manchester, UK.; Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK., Butcher I; Institute of Human Development, University of Manchester, Manchester, UK.; Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK., Dunn WB; Institute of Human Development, University of Manchester, Manchester, UK.; Manchester Centre for Integrative Systems Biology, University of Manchester, Manchester, UK.; School of Biosciences, University of Birmingham, Birmingham, UK., Stevens A; Institute of Human Development, University of Manchester, Manchester, UK.; Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK., Perchard R; Institute of Human Development, University of Manchester, Manchester, UK.; Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK., Hanson D; Institute of Human Development, University of Manchester, Manchester, UK.; Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK., Whatmore A; Institute of Human Development, University of Manchester, Manchester, UK.; Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK., Westwood M; Institute of Human Development, University of Manchester, Manchester, UK.; Maternal and Fetal Health Research Centre, University of Manchester, Manchester, UK., Clayton PE; Institute of Human Development, University of Manchester, Manchester, UK.; Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK.
Jazyk: angličtina
Zdroj: Pediatric research [Pediatr Res] 2016 Aug; Vol. 80 (2), pp. 299-305. Date of Electronic Publication: 2016 Apr 08.
DOI: 10.1038/pr.2016.72
Abstrakt: Background: Later life metabolic dysfunction is a well-recognized consequence of being born small for gestational age (SGA). This study has applied metabolomics to identify whether there are changes in these pathways in prepubertal short SGA children and aimed to compare the intracellular and extracellular metabolome in fibroblasts derived from healthy children and SGA children with postnatal growth impairment.
Methods: Skin fibroblast cell lines were established from eight SGA children (age 1.8-10.3 y) with failure of catch-up growth and from three healthy control children. Confluent cells were incubated in serum-free media and the spent growth medium (metabolic footprint), and intracellular metabolome (metabolic fingerprint) were analyzed by gas-chromatography mass spectrometry.
Results: Nineteen metabolites were significantly altered between SGA and control cell lines. The greatest fold difference (FD) was seen for alanine (fingerprint FD, SGA: control 0.3, P = 0.01 and footprint FD = 0.19, P = 0.01), aspartic acid (fingerprint FD = 5.21, P = 0.01), and cystine (footprint FD = 1.66, P = 0.02). Network analysis of the differentially expressed metabolites predicted inhibition of insulin as well as growth (ERK) signaling in SGA cells.
Conclusion: This study indicates that changes in cellular metabolism associated with both growth failure and insulin insensitivity are present in prepubertal short children born SGA.
Databáze: MEDLINE
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